Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder

Summary & key facts

This review looked at studies that tried to find things you can measure before treatment that predict whether people with treatment-resistant depression (either within major depression or bipolar disorder) will get better after a single dose of ketamine. The researchers found many possible predictors across different areas — body measures, blood tests, sleep patterns, brain chemistry and scans, genes, and thinking speed — but no single, reliable rule yet. Two of the findings showed up most often: higher body mass index and a family history of alcohol problems. The authors say metabolic and inflammation-related signs, and problems with thinking speed, are promising leads, but more data and smarter analysis methods are needed before this can guide treatment for people.

Key facts:

• The paper is a narrative review that collected studies looking for traits measured before treatment that predict ketamine response in treatment-resistant depression within major depressive disorder and bipolar disorder.
• Researchers found many types of possible predictors, including clinical measures, blood chemistry, sleep recordings, brain chemistry, brain scans, genes, and thinking-speed tests.
• Higher body mass index (BMI) and a family history of alcohol use disorder were the two findings that appeared most often across studies as linked to better response to ketamine.
• Certain blood markers were linked to response. The review names adiponectin and vitamin B12 levels as examples of blood measures that showed associations in some studies.
• Sleep measurements mattered in some studies. Abnormalities in the delta sleep ratio, a measure from sleep recordings, were linked to ketamine response in some cases.
• Brain-based measures were also reported. Activity in the anterior cingulate cortex (a brain region involved in emotion) and the balance of glutamine to glutamate (brain chemicals) were associated with response in some studies.
• A genetic variation called Val66Met in the BDNF gene was reported as a possible predictor in some work.
• Slower processing speed — a simple measure of thinking speed and attention — emerged as a possible predictor, which points to cognitive problems being important.
• The authors emphasize that a clear clinical profile of who will benefit from ketamine is not yet established. They suggest that complex, data-driven methods that test many factors together are likely needed to make useful predictions for people.

Abstract

OBJECTIVES: Extant evidence indicates that ketamine exerts rapid antidepressant effects in treatment-resistant depressive (TRD) symptoms as a part of major depressive disorder (MDD) and bipolar disorder (BD). The identification of depressed sub-populations that are more likely to benefit from ketamine treatment remains a priority. In keeping with this view, the present narrative review aims to identify the pretreatment predictors of response to ketamine in TRD as part of MDD and BD. METHOD: . RESULTS: Multiple baseline pretreatment predictors of response were identified, including clinical (i.e., Body Mass Index (BMI), history of suicide, family history of alcohol use disorder), peripheral biochemistry (i.e., adiponectin levels, vitamin B12 levels), polysomnography (abnormalities in delta sleep ratio), neurochemistry (i.e., glutamine/glutamate ratio), neuroimaging (i.e., anterior cingulate cortex activity), genetic variation (i.e., Val66Met BDNF allele), and cognitive functioning (i.e., processing speed). High BMI and a positive family history of alcohol use disorder were the most replicated predictors. CONCLUSIONS: A pheno-biotype of depression more, or less likely, to benefit with ketamine treatment is far from complete. Notwithstanding, metabolic-inflammatory alterations are emerging as possible pretreatment response predictors of depressive symptom improvement, most notably being cognitive impairment. Sophisticated data-driven computational methods that are iterative and agnostic are more likely to provide actionable baseline pretreatment predictive information.

Topics

Bipolar Disorder and Treatment Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Alcohol Alcohol use disorder Antidepressant Anxiety Biochemistry Bipolar disorder Chemistry Clinical psychology Internal medicine Ketamine Major depressive disorder Medicine Mood Neurochemistry Neurology Oncology Psychiatry Psychology

Substances

Ketamine

Conditions & symptoms

Anxiety Difficulty focusing Lack of energy or motivation Poor sleep Sadness or low mood